Development of a Universal PAT Interface for Drug Product Manufacturing Processes

Universal PAT interface enables spectroscopic measurements for a variety of unit operations

Abstract Text:

Continuous manufacturing processes often have Process Analytical Technology (PAT) sampling locations designed into them from the start, enabling continuous monitoring of critical quality attributes such as blend potency, moisture content and particle size distribution.  However, for existing equipment e.g. those used for established batch processes, the addition of PAT capabilities can require significant investments for modification and requalification of the various unit operations.  A cost-effective approach is to design and install a PAT interface that can be easily attached between unit operations and can operate independently.  For example, the interface could be installed between an Intermediate Bulk Container (IBC) and a tablet press, enabling high-quality, real-time, in-line measurements of the powder stream.  Principally, such an interface should present powder consistently to the PAT probe, operate under a variety of throughputs and maintain as much as possible, plug-flow behavior within the down-flow pipe (so as to not introduce segregation, or excessive shear or lubrication).

 
In this work, a Universal PAT interface was designed with a central impeller to convey powder past a PAT probe, and tri-clamp-compatible fittings so it can attach in-line along the central axis, to any down-flow pipe.  Rapid prototyping was accomplished via 3d-printing to produce fully functional versions, and experiments were performed to optimize the angle of the PAT probe, test the maximum throughput, assess the interface’s capabilities as a science-of-scale tool, and test the performance of interface on a tablet press.  The outcomes of these experiments were used to inform the design of a stainless-steel version suitable for use in development and GMP manufacturing.  Using the same device for laboratory-scale experiments as well as clinical and commercial manufacturing expedites process understanding, de-risks process development (e.g. to detect segregation for given formulations) and accelerates PAT method development and deployment.